About BREACH

Overview

The correlation between tumour biology and the coagulation cascade is being investigated with increasingly marked interest. The BREACH study was designed to assess the clotting profile and proteomic characteristics in breast cancer patients pre, post and during treatment in order to provide better insight in the biology of cancer. This pilot study will pave the way to large trials to explore a correlation between important clinical indicators such as survival and response to therapy.

Clinical Need

Venous thromboembolism (VTE) is a relatively common and serious event in individuals with malignancy. Its occurrence complicates the clinical care of the patient and can have a profoundly negative impact on an already compromised quality of life.

Unfortunately, both the prevention and treatment of blood clots increase the risk of bleeding. Better understanding of blood clot risk and treatment in patients with cancer undergoing chemotherapy will help to improve prevention and quality of life in these patients.

Cancer patients receiving chemotherapy do not routinely receive antithrombotic prophylaxis unless they have a history of VTE. This is probably because there is a perception that the risk is low and prophylactic methods are logistically complicated. It may be possible however to identify a group of cancer patients at very high risk of VTE (risk stratification) for whom oncologists would agree that prophylaxis is warranted.

Status

Recruitment has now been closed and data collection has now been completed. All samples have been analysed. Data is being transferred to the study statistician for statistical analysis.

Study Details

BREACH is a prospective, single centre study of patients with newly diagnosed breast cancer, designed to apply basic science which will help to enhance human health and well-being by improving management and treatment in breast cancer patients.

Findings from BREACH will help to improve management and treatment in these patients.

Rationale

Venous thromboembolism (VTE, blood clots in the blood vessels) is estimated to be the second most common cause of death in cancer patients, with up to 60% of those deaths occurring at an otherwise favourable time in the history of the cancer. Cancer patients are also known to be more susceptible to bleeding complications either due to the cancer itself or its treatment.

In one study, it was estimated that one in seven cancer patients will die of potentially avoidable pulmonary embolism (PE) rather than cancer itself. There is good evidence that post-operative thromboprophylaxis is effective and safe in cancer patients undergoing surgery.

The results of the CLOT trial have shown the superiority of long-term low molecular weight heparin (LMWH) over warfarin in cancer patients with acute VTE. Interestingly, a subgroup analysis showed a better survival in patients receiving 6 months thromboprophylaxis with LMWH when compared to warfarin. The FAMOUS Study showed an increase in median survival in patients with advanced malignancy receiving LMWH compared to placebo. A study on patients with small cell lung cancer showed a significant survival advantage in patients receiving LMWH in combination with their chemotherapy. Finally, the MALT study showed a marked survival advantage in patients with solid tumours receiving LMWH when compared to placebo.

We recognised the need for a study to provide data on the biomarkers of coagulation in cancer patients and the relationship with VTE.

Study Design

BREACH is a prospective study of subjects with newly diagnosed breast cancer fulfilling the inclusion/exclusion criteria. Patients were treated according to local best practice, and this study, or ‘both the exclusion and inclusion’ did not entail any experimental intervention. Blood samples were collected from the patients according to the protocol with no additional procedures required by the study. Samples collected at the baseline, chemotherapy and post-treatment stages were used to assess the coagulation profile, proteomics assays and platelet micro-particles.

The progression after diagnosis and changes since baseline have been monitored for:

Acute venous thromboembolism

Bleeding complications

Central venous catheter

Chemotherapy

Death

Hormonal therapy

Peripheral arterial thrombosis

Post-operative staging

Radiotherapy

Surgical treatment

Suspicion of venous thromboembolism

Venous thromboembolism prophylaxis

Vascular incidents

Study Population

All patients with a newly histological diagnosis of breast cancer stage 2 or higher expected to receive treatment with chemotherapy were considered for enrolment. For this pilot study the sample size of 100 has been determined by practical considerations.

Each recruited patient had to meet the study criteria and had to have given consent.

Inclusion Criteria

An answer of “no” to any of the following excludes the subject from entering the study.

Data Collection

Blood samples were collected from the patients according to the protocol with no additional procedures required by the study. Selected data were collected from the patients’ clinical records according to the specification in the case report form (CRF). Patient progress was monitored for up to 2 years, with special attention to medical history, thromboembolic risk factors, treatment and outcome. Blood samples were used to assess the coagulation profile, proteomics assays and platelet micro-particles.